Computer modeling is based on molecular dynamics (MD) conformational of opioid peptides in solution. Visualization permits inferences to be drawn on changes in the dihedrals in the backbone, chirality and side-chain of the constituent residues with direct impact on peptide binding. Knowledge gained from understanding the mechanisms of these interactions are essential for a rational approach to designing new peptides with agonist and antagonist activity. Modeling used various programs, such as MacroModel, Spartan, Hyperchem and AMBER, PC-based and Unix systems (Silicon Graphics). MD simulations on the 3 natural deltorphins indicated a relationship between delta affinity and conformation: deltorphin B is a more compact than deltorphins C or A with the latter two being more extended; all peptides exhibit -turns in their N-termini. D-Asp4 and Pro4 alter chirality and backbone conformation and modified the spatial conformation to resemble deltorphin B and enabled interaction with the same subset of delta opioid receptors. Length of the side-chain at position 4 affects intramolecular H bonding and accounts for differences in conformation. Simulated annealing indicated that peptides with -turns possessed lower energies than those with extended conformations; turns in the N-terminal region appear are linked to delta receptor affinities. Higher energy conformations derived from the lowest energy clusters illustrated that analogues with extended topographies fit 1-site binding models, while those with multiple turns fitted a 2-site binding model. An hypothesis on opioid peptide conformation suggests differentiation between delta-1 and delta-2 receptor subtypes as well as agonists and antagonists; hydrodrophobic side-chains in position 2, 3 or 4 modulate peptide conformation, and affect affinity and selectivity.